A therapeutic cancer vaccine targeting carcinoembryonic antigen in intestinal carcinomas.
A genetic vaccine platform based on DNA electroporation (DNA-EP) and adenovirus (Ad) was used to generate immune response against human carcinoembryonic antigen (CEA) and antitumor effects in murine models with spontaneous tumors arising in an orthotopic location. CEA transgenic (CEA.Tg) mice treated with the carcinogen 1,2-dimethylhydrazine developed CEA-overexpressing tumors that resembled human sporadic colorectal cancer. APC1638N/CEA hybrid mice, generated by crossing mice carrying the adenomatous polyposis coli (Apc1638N) gene mutation with CEA.Tg mice, are representative of human familial polyposis and develop polyps that overexpress the antigen. In both models, the DNA-EP/Ad vaccine succeeded in breaking immune tolerance and achieved significant antitumor effects in therapeutic settings. Our data suggest that genetic vaccines targeting CEA may be feasible strategies against gut tumors that overexpress the antigen. In addition, these models are powerful systems for evaluating antigen-specific tumor immunity and assessing therapeutic vaccine strategies for human colorectal cancer.
Mori
Federica
F
Department of Oncology, Istituto di Ricerche di Biologia Molecolare (IRBM), Merck Research Laboratories, Pomezia (Rome), Italy.
Giannetti
Patrizia
P
Peruzzi
Daniela
D
Lazzaro
Domenico
D
Giampaoli
Saverio
S
Kaufman
Howard L
HL
Ciliberto
Gennaro
G
La Monica
Nicola
N
Aurisicchio
Luigi
L
D018256:Adenomatous Polyps / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012015:Reference Standards; D015854:Up-Regulation
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen